Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
124 Cards in this Set
- Front
- Back
|
what are definig characteristics of shock
|
1. hypotension
2. acedemia 3. hypoperfusion 4. hypoxia, decreased ATP |
|
|
what causes cardiogenic shock
|
failure of pump
**MI, arrythemia, inflammation, cardiomyopathy |
|
|
what causes obstructive shock
|
decreased blood return to heart
1. tension pnemothorax (pressure in thorax compresses vena cava) 2. Cardiac Tamponade (pressure on vena cava decreases return) 3. PE, embolism blocks blood from entering R ventricle 4. tumor in L vent |
|
|
what causes hypovolumic shock
|
1. burn
2. bleed 3. diarrhea 4. dehydration **decreased Cardiac Output because of decreased volume |
|
|
what causes anaphylatic shock
|
type 1 hypersensitivity, IgE
histamine causes massive vasodilation, all the blood pools in extremities nad doesnt return to the heart |
|
|
what are some clinical signs of anaphylatic shock
|
dyspnea
tachypenea swollen airway tachycardia confusion type 1 hypersensitivity, IgE histamine causes a huge vasodilation |
|
|
what are some signs adn sx of shock
|
1. cool clammy pale skin (except sepsis is warm and dry)
2. cyanosis at mouth and fingers/toes 3. tachycardia, weak pulse 4. tachypena (get rid of acidemia) 5. confused |
|
|
what is the HR in shock
|
fast with a weak pulse
|
|
|
fever and leukocytosis indicates what
|
infection
**ggram + is common for septic shock |
|
|
what would happen to BP, urine output, and kidney fx with shock
|
1. BP decreased bc of low volume
2. urinde decreased to save volume 3. renal failure ???????????????????? |
|
|
what are some things that will cause septic shock?
|
gram +
gram - bacilli fungi virus |
|
|
sepsis activates what part of the immune system
|
innate
TLR4 binds to LPS and causes MASSIVE vasodilation that causes blood to pool and HYPOperfusion occurs. **skin is WARM and DRY (contrast to cool clammy seen in other shock) **pt has fever |
|
|
in septic shock we have bacterial constituents doing what?
|
1. Activate Compliment: C3a C5a C3b
2. Activate inflammatory mediators on leukocytes (TNF IL1 HMGB1) 2. Coagulation Factor XII activation: leads to thrombus that blocks even more O2 |
|
|
what are the inflammatory mediators that are activated in septic shock
|
IL1
TNF a HMGB1 **also compliment C3a, C5a, and C3b **leads to dilation --> pooling of blood --> hypoperfusion |
|
|
what is the sequelae to septic shock
|
vasodilation
increase cap permiability thrombosis **all of these things cause even LESS O2 to reach tissues |
|
|
so we know inflammation occurs initially in septic shock, is this maintained
|
nope, we eventially get IL10 and lymphocyte apoptosis that shifts to a more ANTI inflammatory
|
|
|
does septic shock lead to acidosis or alkalosis
|
acidosis, low O2 so anerobic glycolysis and LACTIC ACID production
**lactic acidosis |
|
|
when do we see anti-inflammatory in septic shock
|
once we are in full blown shock its through weve switched to ANTI inflamm via IL10 and leukocyte apoptosis
|
|
|
what organ dysfx is seen with septic shock
|
Lungs: Acute Respiratory Distress Syndrome (ARDS)
Heart: cardiac dysfx Liver: HYPOglycemia Acute Kidney Injury (renal tubular necrosis) seen in ALL causes of shock |
|
|
is the kidney damaged in all cases of shock
|
yep, all causes of shock lead to renal dysfx (acute kidney injury, renal tubular necrosis)
|
|
|
what are the phases of shock, do all types of shock go through the phases
|
1. Non Pregressive
2. Progressive 3. Irreversible **NO stages seen in septic shock |
|
|
what is teh non progressive phase of septic shock
|
TRICK< no phases of septic
1. Non progressive 2. Progressve 3. Irreversible |
|
|
what is the nonprogressive phase of shock
|
1st stage
**we have mechs to maintain CO nad BP -kidneys maintain H20 -SNS causes constriction via NE a1 Receptors --> tachycardia and increased peripheral resistance |
|
|
what is the progressive phase of shock
|
2nd stage
*tissue hypoxia so we get lactic acidosis, the acidemia blunts the vasomotor response and instead of constriction we get dilation of BV. This leads to blood pooling and decreased CO. Kidneys begin to fail and we get endthelial damage to BV. |
|
|
at what pt is shock irreversible?
|
irreversible stage, stage 3 (non progressive, progressive, irreversible)
*lysosomes burst and degrade cellular contents *kidney shuts down --> acute tubular necrosis *destroy myocardial contractility **bc all the cells are bursting that GI flora enters circulation and ends up septic |
|
|
what cells have the hardest time recovering from shock
|
cardiomyocytes
neurons **most tissue can recover. best recovery in hypovolumic shock in young **worst prognosis for septic and cardiogenic shock |
|
|
what is DIC
|
disseminated intravescular coagulation
**thrombi that from as a result of shock. clinically leads to bleeding |
|
|
what is the morphology of shock to organs
|
1. kidney: acute tubular necrosis
2. Lungs: ARDS, alveolar damage 3. Heart adn Liver: steatosis, necrosis 4. GI: hemorrhagic necrosis 5. DIC (thrombi that leads to bleeding) |
|
|
what is an imporforate anus
|
failure of anal membrane to apoptose
|
|
|
is there an inflammatory response in apoptosis? necrosis?
|
apoptosis: not really, PHAGOCYTOSED BY NEIGHBORING CELL
necrosis: YOU BET!!! |
|
|
is the stimulus what determines if a cell will apoptose or necrose?
|
nope, same stimuli for both processes
|
|
|
what are some characteristics of Apoptosis
|
1. pathologic or physiologic
2. programmed cell death 3. E dependent, requires ATP 4. Lysosomes remain in tact, membrane integrity maintained 5. single cell eliminated and phago by neighboring cell 6. No inflammatory |
|
|
what does it look like when a cell apoptoses
|
shrinks, chromatin condenses and FRAGMENTS
**apoptotic bodies from blebs **single cell, **no inflammatory response |
|
|
where does TONS of physiologic apoptpsos occur
|
thymus
kill self T cells **nucleus fragments, pyknotic |
|
|
what are some physiologic causes of apoptosis
|
1. infected or mutant cells
2. senescent cells 3. embryo (aortic arch, mesonephros) 4. control tissue that divieds (epithelium, hematopoiesis) 5. breast, vagina, endometrium at menopause (hormone dependent) 6. remove inflammatory cells |
|
|
how can you distuinguish apoptosis and necrosis on electrophoresis
|
Apoptosis: DNA FRAGMENTS seperate out and make a ladder
Necrosis: makes a smudge |
|
|
what is the intrinsic (mito) path of apoptosis?
when do cells apoptose? |
1. in a SINGLE cell caspase cleaves cytoskeleton (shrink) and activate DNAse (fragmented DNA ladder). the cells is then cleaned up my neighboring cells
seen in embryogenesis, atrophy of menopause, hormone induction (menstruation) result of: injury, release of cyto C into cytosol |
|
|
in what type of cell death are caspases activated to cleave the cytoskeleton and DNAase break up DNA
|
intrinsic (mito) path of apoptosis
|
|
|
how are cells undergoing apoptosis removed/
|
phago be neighbors or macro
1. Phosphatidylserine from the membrane moves to the surface and is recognizzed by phogocytizer 2. apoptotic cell may be covered in compliment 3. cell is cleared quickly |
|
|
waht is the stimulus for intrinsic path apoptosis
|
injury, cytochrome C in cytosol, normal processes like embryogenesis, atrophy of menopause and hormone induction of endometrium
|
|
|
what is te eextrinsic path of apoptosis
|
1. FasL:
2. CTL: perforin and granzyme |
|
|
what is teh "death receptor initiated" pathway of cell death
|
the extrinsic apoptotic path
|
|
|
what can bind to a "death domain" and what type of cell death is initiated
|
TNF or FAS
**when ligand binds caspase 8 is activated and leads to apoptosis extrinsic path of apoptosis |
|
|
where is FAS L found
|
on T cells, so when it binds there is killing of mainly self reactive lymphocytes
|
|
|
what are some T cells apoptosed
|
respond to self AG
inappropriate affinity to AG |
|
|
what are the genes involved in Apoptosis
|
Fas FASL
caspase 8 |
|
|
if the breast looses hormone what happens
|
apoptosis, breasts shrink
|
|
|
extrinsic pathway
|
TNF binds the R and leads to pathyway that activates caspase
FAS FASL same thing but for T cells |
|
|
whats the thing about TNF
|
its part of apoptosis extrinsic pathway
its called tumor necrosis factor but its not invllved in necrosis. perhaps in septic shock it does play a role in necrosis but normally its apoptosis Once bound TNF can have several paths: 1 leads to apoptosis, the other activates NFkB and BLOCKS apoptosis |
|
|
what does NFkB do and what stim it
|
blocks apoptosis
**TNF can activate NFkB and block apoptosis but TNF can also initiate apoptosis |
|
|
when we see cytochrome C we think what kind of cell death
|
apoptosis
intrinsic (mito) pathway |
|
|
what is the stimuli for intrinsic apoptosis
|
1. remove hormones
2. DNA damage 3. Cytochrome C released from mito and chillin in cytosol (cyto C activates caspase 9) |
|
|
we know that the intrinsic path is initiated with DNA damage, how does this haooen
|
p53 accumulates and stops cell cycle to let the cell heal itself, it if can fix the damage we get BAX and the cell dies via apoptosis
**cancer with mutated p53 are really hard to treat bc it cant initiate apoptosis |
|
|
what is BAX
|
the signal the cell gets to do apoptosis
**intrinsic path: there is DNA damage so p53 pops up and tells the cell cycle to stop so it can repair the DNA, if the DNA cant be repaired we get BAX and BAX tess us to kill that cell via intrinsic apoptosis **type of Bcl family |
|
|
what is bcl 2? what happens wth overexpression
|
bcl: b cell lymphoma family with homologous domains. can be pro or anti apoptotic
Overexpression of bcl 2 means the cell cant die, its anti apoptotic BAX nad Bak are PRO apoptotic Bcl2 bclx and mcl 1 are ANTI apoptotic |
|
|
how are BAX nad Bcl2 involved in apoptosis
|
intrinsic path
BCL2 wont let cyto c out: antoapoptotic. Cell LIVES BAX: lets cyto C out, PRO apoptotic/ CELL DIES |
|
|
how is CTL mediated apoptosis done
|
perforin (makes a hole in membrane) and granzyme
**kills cells with virus or cancer cells |
|
|
what uses perforin and granzyme
|
CTL for apoptotic killing
|
|
|
what are apoptotic inhibitors
|
1. NFkB
2. BCL2 3. GF, sex hormones 4. FLIP- inhibit caspase 8 5. IAP- inhibit caspase 3 |
|
|
tell me everything about NFkB
|
1. TF
2. Proinflammatory, makes IL2 3. Cell SURVIVAL via Bcl-x 4. Negatively regulated by IkB |
|
|
does ischemia lead to necrosis or apoptosis
|
either one!
|
|
|
what happens with viral hepatitis and HIV?
|
we get disease bc of excess apoptosis
**also see excess apoptosis in: -spinal mm injury -neurodegenerative disease -ischemic injury (MI, stroke) |
|
|
so we can get disease bc of excess apoptosis (HIV, viral hepatitis, ischemia, neurodegenerative)
when do we get disease due to lack of apoptosis |
autoimmune disease: dont kill autoreactive T
Tumor with anti apoptotic things like Bcl1, NFkB, or mutated p53 Viral Infections (Epstein Barr) |
|
|
what would happen if a tumor expressed Bcl1 NFkB or mutated p53
|
it wowouldnt die!!! pathology due to deficient apoptosis
**Bcl1 and NFkB inhibit apoptosis **when p53 is mutated it cant stop the cell cycle and fix DNA damage and initiate BAX to kill if needed so the cells all just live---CANCER |
|
|
what is hemosiderin?
|
Hg derived bits of Fe that is left over
**can be used to ID bruising. small amts usually found in liver, spleen and bone marrow but localized hemosiderin accumulations means there was some hemmorage/bruise **stains with PRUSSIAN BLUE |
|
|
wht is prussian blue used for
|
to stain hemosiderin
fe accumulations |
|
|
are small amts of hemosiderin or large localized accumulations normal
|
small amts in bone marrow, liver and spleen, are ok
large localized amts means bruising or hemmorage inthat ares **its Hg derived Fe left overs, visualized with prussian blue |
|
|
what are the 2 forms of Fe overload
|
1. Hemosiderosis: Fe in parenchymal cells with no organ dyxfx
2. Hemochromatosis: MASSIVE Fe accumulation, leads to organ damage. cirrhosis |
|
|
what is it called if you have some small amts of Fe accumulation w/o organ damage? what about MASSIVE amts of Fe with organ damage or cirrhosis
|
Small amts: hemosiderosis
LOTS: hemochromatosis |
|
|
what is hemosiderosis, what is hemochromatosis
|
hemosiderosis: little Fe build up in parynchmeal cells. no damage
Hemochromatosis: MASSIVE Fe build up with organ damage |
|
|
so we have 2 Hg derivatives that can build up, whats the one with Fe, what about without
|
With Fe, hemosiderin
W/O: biliruben, jaundice/icterus |
|
|
what is Kernicterus
|
bulidup of uncong biliruben in brain of young infants
|
|
|
what is the excess accumulation of biliruben called
|
jaundice
icterus |
|
|
this is the morphology of what? mucoid, green-brown to black globular deposit
|
biliruben, Fe free derivative of Hg.
called jaundice or icterus when in excess |
|
|
what are the 2 types of pathologic calcium deposition
|
1. Dystrophic: serum Ca levels are normal but damaged tissue gets Ca deposits
2. Metastatic: hypercalcemia or hyperphosphatemia causes normal tissue to get calcification |
|
|
name that calcification...
1. high Ca levels cause non pathologic sk mm to get calcification 2. diseased heart mm is calcified even though normal Ca levels |
1. metastatic: this is when high Ca or K levels in the blood lead to deposition of Ca in healthy tissue
2. dystrophic calcification: lay Ca in abnormal tissue even when serum Ca is normal |
|
|
what are some things that can increase your likelyhood to have dystrophic calcification
|
dystrophic: normal Ca, tissue is nonviable
-necrossis: coagulative, liquefative, caseous, fat -atherosclerosis -aging -danaged heart valves -breast in fibrocystic change and in situ carcinoma |
|
|
what is teh gross and micro morphology of dystrophic calcificaiton
|
gross: fine white granules, hard
Micro: lots of purple granules, heteropic bone formation |
|
|
what are some things that will cause hypercalcemia and hyperphosphatemia. what can this then lead to?
|
increased Ca can be due to hyperparathyroidism (increased PTH), increased bone destruction,
Hyperphosphatemia can happen with renal failure **the increase in Ca and K will lead to metastatic calcification (normal tissue will get Ca deposits) |
|
|
where do we often see metastatic calcifications
|
kidney, lung, GI
|
|
|
is cellular aging a disease state?
|
nope, its a natural process
results from decline in porliforative ability, and accumulation of damage |
|
|
what are 4 things that can lead to cellular aging.
|
1. Telomere shortening
2. Environmental Insults 3. Defects in DNA repair 4. Abnormal GF |
|
|
what in one way to delay cellular agind
|
calorie restriction
**Sirtuin proteins are activated |
|
|
in what ways are DNA damaged as a cell ages
|
1. normal replication
2. free radical damage 3. defects in DNA repair |
|
|
what is hutchinson Gliford Syndrome
|
premature aging disease,
**defect in LMNA gene |
|
|
what is replicative senesenence?
|
decreased cellular replication, arrested, terminally non dividing state
**happens in all cells, bc of short telomeres **telomerase only on germ cells, stem cells and cancer cells |
|
|
where is telomerase?
|
in stem cells, germ cells, and cancer cells
**in all other cells we have telomers htat shorten adn eventually get so short they can no longer replicate |
|
|
can a cell with no telomere divide?
|
nope, it needs telomerase, the only cells with telomerase are stem, germ, ad cancer
|
|
|
what does telomerase do
|
extend 3' end of DNA during replication to be sure the temomeres stay long and can divide lots and lots
**telomerase is only found in germ, stem, and cancer cells. all other cells will get such short telomeres they can no longer divide |
|
|
What are 4 mechs of intracellular accumulations?
|
1. Abnormal metabolism as seen in fatty liver. 2. Protein mutation that inhibits folding or transport, seen in a1antitrypsin defect. 3. Deficient enzymes, seen in lysosomal storage disorder. 4. Inability to degrade foreign material that is phagocytized, as seen in hemosiderosis and coal inhalation.
|
|
|
Fatty liver is an example of what mech of accumulation?
|
Normal substance that is made at an increased rate or there is just inadequate metabolism for removal, fat accumulates in cytosol
|
|
|
What can happen if protein is mutated such that it cant be folded?
|
It wont be able to be transported and it will accumulate in the ER
|
|
|
What happens if we lack an enzyme required for metabolism?
|
Accumulation of intermediates. Seen in lysosomal storage disease
|
|
|
What happens when cells take up exogenous substances that really aren’t supposed to be there?
|
They accumulate bc the cell doesn’t have the necessary things to remove it
|
|
|
Case: old man who lived in Phx was killed by a car, non smoker with subpleural reticular pattern of net like pigmentation. What is the pigment? How did the pigment get there? Where else might you see this pigment? What are risk factors for increased amts of this pigment?
|
Its anthrasosis. Inhaled carbon that is taken up by macrophages and reached the lungs via subpleural and mediasteinal lymphatics. You may also see the anthracosis in lymph nodes. Increased risk for getting coal in lungs for ppl in pollution, smokers, coal miners, and ppl who cook over open flame
|
|
|
What is steatosis? Where does it happen? Is it reversible?
|
Fatty change due in accumulation of Triglycerides. Common in liver and heart, can also be seen in mm and kidney. Reversible, caused by obesity, DM, EtOH, carbon tet, shock/anoxia, protein malnutrition, rapid weight loss
|
|
|
What can these things cause: Obesith, EtOH, DM, CCl4, protein malnutrition, rapid weight loss, shock/anoxia?
|
Hepatic steatosis, fatty liver due to accumulations of triglycerides. We can also have steatosis of the heart, mm, and kidney
|
|
|
What is the pathogenesis of steatosis?
|
Accumulation of triglycerides can be due to: 1. Increased Fat/mobilization- obesity, DM, starvation 2. Decreased TG acceptors-malnutrition, CCL4 3. Decreased mito oxidation- anoxia (heart failure/shock) 4. Mito defects- EtOH
|
|
|
Why does starvation lead to steatasis?
|
We begin to mobilize fat stores and the liver cant handle it. This is also seen in obesity and DM
|
|
|
Why can malnutrition and carbon tet lead to steatosis?
|
Decreased synthesis of fat acceptors so the fat accumulates
|
|
|
Why can the anoxia seen in heart failure lead to steatosis?
|
Decreased oxidation in mito so fat can accumulate
|
|
|
Why does excess EtOH lead to fatty liver?
|
EtOh damages the mito, damaged mito cant oxidize fat like its supposed to
|
|
|
How can we tell if someone has fatty liver?
|
AST nad ALT are elevated. Steatosis can be reversed but it can also progress into cirrhosis
|
|
|
If someone has elevated AST ALT and a hx of obesity and EtOH abuse what may their autopsy reveal? What about a CT? what about microscopic?
|
Fatty liver: enlarged, greasy and yellow. On CT the liver will look homogenous and less dense. Micro: lots of white lipid drops.
|
|
|
What are the causes of hepatic steatosis?
|
Obesity, DM, EtOH, CCl4, protein malnutrition, rapid weight loss, shock/anoxia
|
|
|
Describe the morphology of hepatic steatosis
|
Large yellow greasy liver. Homogenous and decreased density on imaging. Micro there are lots of fat drops
|
|
|
What are the clinical consequences of hepatic steatosis?
|
Elevated ALT AST, can be reversible or can impair cell fx and lead to cirrhosis/steatohepatitis
|
|
|
Wht happens to cardiomyocytes when damaged via hypoxia?
|
Cell swells and accumulates fat. Without O2 you cant properly metabolize fat and so it accumulates
|
|
|
When we get lipid accumulation in cardiac mm what are the 2 ways it can look and what causes each?
|
. Tiger- yellow bands that alternate with unaffected tissue. Caused by prolonged moderate hypoxia, think anemia
2. Uniformly affected: all mm is affected. Caused by profound hypoxia as seen in shock, maybe also toxic injury like diphtheria |
|
|
What is a foam cell?
|
Macrophage with lots of cholesterol accumulations. Can be found in BV wall and its called atheroschlerosis or in the skin/tendons and are called xanthomas. Seen in neiman pick disease
|
|
|
What are the 2 locations a foam cell can be found?
|
Atherosclerosis: found in BV wall, can also have free cholesterol present. Xanthomas: foam cell tumors found subdermal, neimann pick C,
|
|
|
What might happen if someone has lots of protein in their urine?
|
We might seen protein accumulations in the prox conv tubule
|
|
|
What might happen with an alpha1 antitrypsin defect?
|
Accumulation of Misfolded protein in the ER
|
|
|
Why might we see lots of dense eosioniphilic spots in the renal tubule?
|
If the glomerulus is leaking LOTS of protein we might get protein accumulations in the renal tubule. We would also prbly see protein in the pee
|
|
|
If you see a homogenous pink smudgy thing on H and E what are you looking at?
|
Hyaline change, its protein accumulation. Can be intra or extracellular. Hyaline change is just a general descriptor
|
|
|
What are some examples of intracellular hyaline change? Extra?
|
Intracellular: Mallory alcoholic hyaline bodies, reabsorption droplets in renal tubule. Extracellular: arteriole walls
|
|
|
What are some diseases associated with glycogen accumulation?
|
1. DM: glycogen accumulates in renal tubule, liver cells, myocardial cells. 2. Glycogen Stroage disease/glycogenoses- defect in enzyme
|
|
|
What does it look like on H/E when you see lots of glycogen in the renal tubule cells of a person with DM?
|
lots of glycogen! Clear vacuoles. Need PAS to stain glycogen
|
|
|
Whats the tell tale sign of wear and tear of an old person? Where is it often found?
|
Lipofuscin. Heart and liver
|
|
|
Whats lipofuscin?
|
Pigment that accumulates from wear and tear. Found often in heart and liver
|
|
|
What is lipofuscin made of
|
Insoluble residues that formed from lipid peroxidation (free radical injury)
|
|
|
What is lipofuscin associated with?
|
Old age. Brown atrophy
|
|
|
What is the only normal endogenous brown black pigment?
|
Melanin. Found in basal layer of epidermis to protect replicating cells from DNA damage
|
|
|
Lipid peroxidation by free radicals results in an insoluble residual body called what?
|
lipofuscin
|
